       Document 0274
 DOCN  M9440274
 TI    Inhibition of human B-cell chronic lymphocytic leukemia by a monoclonal
       antibody in xenograft models.
 DT    9404
 AU    Zhu Z; Ghose T; Hoskin D; Lee CL; Fernandez LA; Rowden G; Lee SH;
       Department of Pathology, Dalhousie University, Halifax, Nova; Scotia,
       Canada.
 SO    Int J Cancer. 1994 Feb 1;56(3):439-45. Unique Identifier : AIDSLINE
       MED/94148555
 AB    To establish xenograft models of human B-cell chronic lymphocytic
       leukemia (CLL), we inoculated 5 x 10(6) D10-1 cells, a subline of
       Epstein-Barr virus (EBV)-transformed human B-cell CLL with a marker
       chromosomal anomaly, into SCID or irradiated nude mice by the
       intravenous (i.v.) or intraperitoneal (i.p.) route. All i.p.
       tumor-inoculated mice developed rapidly progressive, lethal ascites
       tumor, and 100% of i.v. tumor-inoculated mice developed disseminated
       CLL. All mice died of tumor within 8 weeks of tumor inoculation.
       Tumor-inoculated SCID mice died earlier with wider tumor dissemination
       than the tumor-inoculated nude mice. All the tumor-inoculated mice had
       histologically confirmed metastases in lymph nodes, and most of them
       also had metastases in one or more internal organs. Cytogenetic analysis
       confirmed the origin of these tumors from the xenografted D10-1 cells.
       The D10-1 cells harvested from the xenografts did not differ from the
       parent D10-1 cells as regards (i) reactivity with 2 monoclonal
       antibodies (MAbs) directed against CLL-associated cell-surface antigens;
       (ii) rate of proliferation in vitro; and (iii) sensitivity to the 2
       chemotherapeutic agents, methotrexate and adriamycin. Administration of
       50 micrograms/mouse of Dal B02, an IgG1 (kappa) MAb directed against
       surface-associated antigens of human B-cell CLL, significantly prolonged
       the survival of D10-1-inoculated nude and SCID mice. The MAb was more
       effective in D10-1-inoculated nude mice than in SCID mice. In all the
       D10-1 xenograft models, the effectiveness of Dal B02 decreased with
       higher tumor load but increased with the amount of MAb injected. Dal B02
       F(ab)'2 fragment failed to demonstrate any anti-tumor activity in
       D10-1-inoculated nude mice. In vitro assays revealed that Dal B02 had no
       direct inhibitory effect on D10-1 cells, but could be cytotoxic towards
       D10-1 cells in the presence of splenic cells or peritoneal macrophages
       from nude and SCID mice, or together with rabbit complement.
 DE    Animal  Antibodies, Monoclonal/*THERAPEUTIC USE  Cell Division  Cell
       Line  Cytotoxicity, Immunologic  Female  Human  Leukemia, B-Cell,
       Chronic/IMMUNOLOGY/PATHOLOGY/*THERAPY  Lymph Nodes/PATHOLOGY  Mice
       Mice, Inbred BALB C  Mice, Nude  Mice, SCID  Neoplasm Transplantation
       Support, Non-U.S. Gov't  Transplantation, Heterologous  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

